The term “heart failure” (HF) as used herein embraces congestive heart failure and/or chronic heart failure as defined by the American College of Cardiology and the American Heart Association as set forth in a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure) authored by Hunt et al. (ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary, J Am Coll Cardiol 2001; 38(7):2101-2113).
Many HF patients exhibit mechanical pulse alternans (MPA), which is a phenomenon wherein alternating mechanical contractions of the heart exhibit alternating values of contraction force or magnitude that cause ejected blood to exhibit like alternating values of diastolic pressure amplitude. MPA has historically be described for the systemic arterial system where alternating high and low arterial pulse pressures have been identified as being related to alternating strengths of contraction (and the resulting stroke volume) of the left ventricle. Similar observations have been described for the pulmonary artery pressure as an indicator of alternating contractile strengths of the right ventricle. MPA has been discussed in the context of increasing heart rate and has been attributed to various functional properties of the heart. See for example: Kodama et al., “Mechanical Alternans in Patients with Chronic Heart Failure”, J Card Fail 2001; 7(2):138-145; Kodama et al., “Changes in the Occurrence of Mechanical Alternans after Long-term Beta-blocker Therapy in Patients with Chronic Heart Failure. Jpn Circ J 2001; 65(8):711-716; and Surawicz et al., “Cardiac Alternans: Diverse Mechanisms and Clinical Manifestations”, J Am Coll Cardiol 1992; 20(2):483-499.
One potential explanation is based on alternate loading conditions of the left ventricle. If the left ventricle contracts strongly and empties well, then the volume of blood left in the left ventricle, i.e., the end systolic volume (ESV), will be nominal. If the heart rate is relatively low, the left ventricle will refill with blood from the left atrium during the next filling phase resulting in a relatively large end diastolic volume (EDV). This larger EDV will, according to Starling's Law of the Heart, cause the left ventricle to more forcefully contract, thereby emptying the left ventricle and resulting in a lower ESV and a relatively large arterial pulse pressure. Then, normal filling added to a lower ESV will result in a lower EDV. The lower EDV on this beat will result in a weaker contraction (by Starling's Law) and less ejection on the next beat resulting in a lower arterial pulse pressure, a larger ESV and the cycle repeats.
Another explanation is that calcium uptake by the sarcoplasmic reticulum is impaired, resulting in less calcium available for the next cardiac cycle. This has been shown in the only animal model of controlled MPA. See Freeman et al, “An Evaluation of Pulsus Alternans in Closed-chest Dogs”, Am J Physiol 1992, 262(1 Pt 2):H278-H284. These observations were made in animals where the preload was lowered using an occluder on the vena cava while the heart rate was maintained at 200 bpm. Importantly, preload is decreasing in this setting while MPA increases. This does not rule out volume changes as important determinants of MPA in patients but does suggest that the alterations in calcium handling may be more crucial to the development of MPA.
Alternate descriptions of MPA are based on other cyclic properties of the cellular mechanisms in the myocardial cells. These mechanisms transfer calcium to and from intracellular storage and release sites and are responsible for the contraction and relaxation of the myocyte. If more Ca++ were available for release, it is expected that the contractile force developed would be greater. The normal cellular Ca++ cycling processes are disrupted by disease, such as HF, and the disrupted processes result in cyclic variations that can be exaggerated, producing hemodynamic variants such as MPA.
Although current pacing systems, incorporated into a pacemaker, e.g., the MEDTRONIC® InSync® Model 8040 pacemaker IPG, or into an ICD IPG, e.g., the MEDTRONIC® InSync® Model 7272 ICD IPG, that provide right and left heart pacing to alleviate HF symptoms collect limited amounts of heart rate data (as well as tachyarrhythmia episode data in the case of ICD IPGs), such data does not always provide sufficient information to assess whether the HF symptoms are being alleviated or are worsening. Nor, do such IPGs presently have the capability of measuring mechanical heart function including MPA and formulating and delivering an appropriate therapy based upon the measured mechanical heart function.
HF patient's hearts frequently exhibit MPA but do not exhibit an abnormal EGM or electrical instability that comprises or is a precurser to a tachyarrhythmia. Hearts of patients that are susceptible to tachyarrhythmia episodes exhibit electrical malfunctions that cause mechanical malfunctions. Malignant tachyarrhythmias, including ventricular fibrillation or flutter (VF) or high rate ventricular tachycardia (VT) cause sudden loss of mechanical heart function and cardiac output that can lead to death unless the heart is cardioverted. Consequently, numerous algorithms have been proposed over the years for use in ICDs to identify tachyarrhythmia episodes, typically from measured rate, onset and stability of the measured EGM through sophisticated signal processing techniques.
In this regard, it has long been postulated that a pattern of beat-to-beat alternation in the amplitude or polarity of the T-wave of the characteristic PQRST complex of the ECG or EGM is indicative of electrical instability and predictive of the susceptibility to tachyarrhythmia as set forth in U.S. Pat. No. 5,265,617, for example. This pattern of alternation, referred to as “electrical alternans” or “T-wave alternans”, is not always present, but often emerges under conditions where the patient's heart experiences an increased demand due to an increased level of physical or mental stress. Electrical alternans can often be measured at the body surface as a subtle beat-to-beat change in the repeating pattern of an ECG waveform. An overview of electrical alternans is given by Rosenbaum, Albrecht and Cohen in “Predicting sudden cardiac death from T wave alternans of the surface electrocardiogram: promise and pitfalls”, Journal of Cardiovascular Electrophysiology, November, 1996, Vol. 7(11), pages 1095-1111.
Thus, episodes of electrical alternans and the heart rates at which the episodes occur have been used to assess patients' risk of developing ventricular arrhythmias. This analysis reflects an alternating pattern of the sequence of electrical depolarization as it spreads through the right and left ventricular chambers. Secondary to this electrical derangement, there may be a variable contraction sequence yielding ventricular and systemic blood pressure alternans patterns similar to MPA even though the myocardial fibers are healthy. Thus, the patient at risk of arrhythmias will exhibit electrical alternans and may or may not exhibit mechanical alternans all because of variation in the propagation paths of the excitatory wavefronts rather than due to impaired myocardial fiber contractility.
It has been asserted in U.S. Pat. No. 6,253,107 that electrical alternans is believed to result from an underlying pattern of alternation in the biochemical processes that drive the functioning of the cardiac muscle. In light of observations of the occasional association of MPA with electrical alternans in hearts susceptible to tachyarrhythmias, it is further asserted that electrical alternans begins to have a measurable effect on the contraction of the muscle cells as the level of electrical alternans increases. An article by Clancy, Smith, and Cohen entitled “A simple electrical-mechanical model of the heart applied to the study of electrical-mechanical alternans”, IEEE Transactions on Biomedical Engineering, June, 1991, Vol. 38(6), pages 551-60, is asserted in the '107 patent as supporting this theoretical relationship between electrical alternans and MPA. The Clancy et al. article noted evidence showing that a subtle electrical alternans observed in the surface ECG may be correlated with the susceptibility to ventricular fibrillation, and offered evidence that MPA generally accompanies electrical alternans. The article indicated that there exists a regime of combined electrical-mechanical alternans during the transition from a normal rhythm towards a fibrillatory rhythm, that the detected degree of alternation is correlated with the relative instability of the rhythm, and that the electrical alternans and MPA may result from a dispersion in local electrical properties leading to a spatial-temporal alternation in the electrical conduction process. This spatial-temporal alternation in the electrical conduction process of electrical alternans is therefore postulated to be the cause of a corresponding MPA detected in the blood pressure waveforms.
It is also asserted in the '107 patent that a healthy heart exhibits a certain level of heart rate variability (HRV) that is evidenced by slightly varying, beat-to-beat heart rates. It is suggested that certain patient's hearts that are susceptible to tachyarrhythmias at times lack such a normal HRV and may exhibit the electrical alternans and/or an alternation in the measured beat-to-beat blood pressure waveform, referred to as “blood pressure alternans” in the '107 patent. A number of IMDs and methods are proposed in the '107 patent that are based on this understanding of HRV and the association of electrical alternans with mechanical alternans in patient's hearts that are susceptible of tachyarrhythmias.
A pacing system is proposed in the above-referenced '107 patent that would periodically pace to overdrive the heart at a slightly varying and random beat-to-beat pacing rate for short time periods to mimic natural HRV. It is also suggested that a measure of cardiac stability, which can be either a measure of electrical alternans or a measure of blood pressure alternans, be developed from the EGM or a blood pressure sensor, respectively, and that the HRV inducing string of pacing pulses can be modified when either measure is present. It is generally suggested that such measure(s) could be employed to either trigger or inhibit or modify the delivery of the pacing pulses to induce HRV. However, no specific examples are provided as to how the intervals between delivered pacing pulses would actually be modified in the presence of either or both of measured electrical alternans and blood pressure alternans or in the absence of both.
A further method is proposed in the above-referenced '107 patent to simply monitor electrical alternans from the EGM and blood pressure alternans from blood pressure measurements in order to assess cardiac electrical stability from both, particularly to identify a heart state susceptible to tachyarrhythmias. The '107 patent does not set forth any explanation of how the cardiac electrical stability is assessed. However, it appears from the reliance upon the Clancy et al. article and the express description that cardiac instability indicating susceptibility to a tachyarrhythmia would be declared when both electrical alternans and blood pressure alternans are simultaneously present.
Thus, a need continues to exist for an IMD that can be programmed to collect meaningful blood pressure data evidencing a mechanical malfunction of the heart, particularly MPA, associated with HF. A need continues to exist for such an IMD that accumulates event data that can be assessed within the implantable monitor stimulator, or an external medical device that the data is transmitted to, to develop a current indicia of the HF state from which the progression of the disease and the assessment of efficacy of prescribed treatment, e.g., programmed parameters of right and left heart pacing, can be assessed.